The investigation is concerned with the effects of drugs and hormones on carbohydrate metabolism of skeletal muscle, heart and other tissues. At present the main approach is a study of uracil nucleotide metabolism in cardiac and skeletal muscle and the actions of insulin and other hormones on the formation of UTP in these tissues. In rat diaphragm insulin has been found to cause a significant increase in the rate of synthesis of UTP from uridine. Since UTP is a reactant in the synthesis of glycogen from glucose, the increase in cellular UTP leads to a marked increase in the ability of the muscle tissue to form glycogen and to respond to insulin. We plan to study the mechanism by which insulin increases UTP formation in muscle and to determine whether uracil nucleotide metabolism in cardiac and skeletal muscle is altered in diabetes.